Human embryonic stem cells for repairing stroke injuries in hippocampal slices.

Funding Type: 
SEED Grant
Grant Number: 
RB2-01645
ICOC Funds Committed: 
$0
Stem Cell Use: 
Embryonic Stem Cell
iPS Cell
Public Abstract: 
Stroke is a medical condition for which we do not have adequate medical treatments. The purpose of this project is to examine the factors that influence the success of using human stem cells to repair injury caused by a stroke (brain ischemia). Because so much remains to be known before stem cell therapies can be used in stroke patients, we propose studies which will create a model of stroke in the laboratory. The model involves slices of the rat hippocampus (a brain region important to learning and memory and very sensitive to stroke damage). A stroke-like insult can be produced in this explanted tissue and cell damage, repair and function of synapses in the tissue can be subsequently followed for long periods of time. The way in which we will examine the effect of human embryonic stem cells is by transplanting them ("seeding") onto the brain tissue in culture. The effects of the stem cells on repairing injury will then be followed over time. Some of the basic questions we will examine include how the specific location in the hippocampus affects the benefit of stem cell application, how the maturity of the stem cells controls neuroprotection, and if we can use new drugs being developed by a biotechnology company (NeuroNascent, Inc.) to improve the benefits of the stem cell therapy. These basic studies are needed to help guide future studies in animals, and eventually, in patients.
Statement of Benefit to California: 
Stroke is a medical condition for which we have limited medical treatments. Repairing the brain following a stroke through the use of human embryonic stem cells offers the potential for improved stroke recovery. This work described in this proposal will address basic questions relating to the best ways to use stem cells to improve stroke recovery. Ultimately, the work will contribute to the health of the citizens of California by fostering the development of new treatments for stroke and related brain diseases.
Progress Report: 
  • The ultimate goal of the proposed study is to identify approaches to increase the production of therapeutically useful blood cells from human ESCs and patient-specific iPSCs. Currently, bone marrow transplantation is the best way to cure many blood-related disorders, such as sickle cell anemia, thalassemia, and blood cancers like leukemia. Furthermore, blood transfusion is an effective way to rapidly counteract blood cell loss due to ablative treatments, such as chemotherapy and radiation therapy. Unfortunately, the limiting factor in transplantation and transfusion treatments is the lack of matched donors. The ability to producing unlimited numbers of blood stem cells and/or functioning differentiated blood cells from human ESCs and patient-derived iPSCs will greatly improve the opportunity of such treatments. Transcription factors play important roles in regulating cell proliferation and differentiation. RUNX1 is a transcription factor that is expressed in blood cells and regulates the expression of many blood cell related genes. Therefore, the specific aim of our studies is to examine the effect of RUNX1 on blood cell formation, expansion, and differentiation from human embryonic stem cells and induced pluripotent stem cells. During the first year of funding period, we have established the cell culture and differentiation systems in our laboratory, generated necessary DNA constructs for the proposed studies, and produced transcription factors for testing the effect.
  • The ultimate goal of the proposed study is to identify approaches to increase the production of therapeutically useful blood cells from human ESCs and patient-specific iPSCs. Currently, bone marrow transplantation is the best way to cure many blood-related disorders, such as sickle cell anemia, thalassemia, and blood cancers like leukemia. Furthermore, blood transfusion is an effective way to rapidly counteract blood cell loss due to ablative treatments, such as chemotherapy and radiation therapy. Unfortunately, the limiting factor in transplantation and transfusion treatments is the lack of matched donors. The ability to producing unlimited numbers of blood stem cells and/or functioning differentiated blood cells from human ESCs and patient-derived iPSCs will greatly improve the opportunity of such treatments. Transcription factors play important roles in regulating cell proliferation and differentiation. RUNX1 is a transcription factor that is expressed in blood cells and regulates the expression of many blood cell related genes. Therefore, the specific aim of our studies is to examine the effect of RUNX1 on blood cell formation, expansion, and differentiation from human embryonic stem cells and induced pluripotent stem cells. During the second year of funding period, we have performed hematopoietic cell differentiation using both human ESCs and iPSCs in the presence and absence of this transcription factor. Our results indicate that this factor promotes the production of blood stem cells and progenitors. We will make additional amount of this factor and further confirm our initial finding.
  • The ultimate goal of the proposed study is to identify approaches to increase the production of therapeutically useful blood cells from human ESCs and patient-specific iPSCs. Currently, bone marrow transplantation is the best way to cure many blood-related disorders, such as sickle cell anemia, thalassemia, and blood cancers like leukemia. Furthermore, blood transfusion is an effective way to rapidly counteract blood cell loss due to ablative treatments, such as chemotherapy and radiation therapy. Unfortunately, the limiting factor in transplantation and transfusion treatments is the lack of matched donors. The ability to producing unlimited numbers of blood stem cells and/or functioning differentiated blood cells from human ESCs and patient-derived iPSCs will greatly improve the opportunity of such treatments. Transcription factors play important roles in regulating cell proliferation and differentiation. RUNX1 is a transcription factor that is expressed in blood cells and regulates the expression of many blood cell related genes. Therefore, the specific aim of our studies is to examine the effect of RUNX1 on blood cell formation, expansion, and differentiation from human embryonic stem cells and induced pluripotent stem cells. During the second year of funding period, we have performed hematopoietic cell differentiation using both human ESCs and iPSCs in the presence and absence of this transcription factor. Our results indicate that this factor promotes the production of blood stem cells and progenitors. We will make additional amount of this factor and further confirm our initial finding.

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